Experiments over the last three years have demonstrated that in the presynaptic terminal of the squid giant synapse the relation between inward calcium current and the synaptic release process is amenable to detailed examination using voltage clamp techniques. The actual relationship of calcium current to transmitter release will be done utilizing double voltage clamp experiments where the pre- and post-synaptic elements of the squid synapse are simultaneously voltage clamped. The purpose of these experiments is to determine the actual time courses of the presynaptic and pootsynaptic currents and thus to establish not only the nature of synaptic delay but, more important, the nature of ionic gain in synaptic transmission. Further study of the voltage-dependent calcium conductance change must be done to obtain information regarding the relationship between membrane potential and calcium current at varying extracellular calcium concentrations. A similar set of experiments will be done to determine the temperature dependence of this process (Q10) as well as on the time course of calcium permeability onset.